Below is a sketchy outline of my many (usually happy) years of research
Over the roughly fourty five years of my scientific activity I was interested in quite a few and rather diverse fields of research. Common to my work in most of these areas has been the approach - namely, applying and developing molecular-level, generally simple, statistical thermodynamic models and theories.
In my MSc and PhD work, under the guidance of professor Shalom Baer at the Hebrew University, I have studied, with and from Shalom, a variety of topics in Equilibrium Statistical mechanics. The MSc work has dealt with the Critical Phenomena and the PhD research with various aspects of van der Waals interactions in liquids, , e.g., the role of non-additive long range forces.
Then, for a short but very intensive period of time - just before leaving for postdoctoral work - I collaborated with Professors Raphy Levine and Richard Bernstein in applying concepts from Information Theory to Chemical Reaction Kinetics, with applications to State-to-State Experiments and Population Inversion in Chemical Reactions.
During the postdoctoral work, together with Professor Ludwig Hofacker from the Technical Uiversity of Munich, but especially with Professor Karl Kompa and his group at the Max Plack Institute for Quantum Optics in Garching, I learned about and focused my research on the theory of Chemical Laser Operation and a variety of Lasers Induced Chemistry phenomena. Returning to Israel in the mid 1970s I continued working on these topics, with Oded Kafri, Shlomit Felix, Amiram Ofir, Eliezer Keren and Benny Gerber, and Micha Baer and Yakir Reuven. Indpenedently I tried to understand and classify the assumptions underlying the different types of Statistical Theories of Chemical Reactions.
In 1980-1982, wishing to learn and work on Biophyical Systems and Phenomena, I spent two fruitful years at UCLA, where together with Bill Gelbart whose scientific background was rather similar to mine, It took us a while before we really started working on biophysical problems. First we learned and became intersted on related, yet more physico-chemical issues, namely Surfactant Self-Assembly and Phase Transitions in Micellar Solutions. With Bill McMullen and other young collaborators we have studied the phase behavior of micellar aggregates, being the first to point out the non-trivial coupling and the crucial role of intra- and inter-aggregate forces in determining the phase behavior of micellar aggregates of different dimensionalities. Our joint research on various aspects of the phase behavior of self-assembled aggregates continued throughout the 1990s in both Los Angeles and Jerusalem, involving our younger collaborators: Jean-Louis Viovy, Didier Roux, Danny Rorman, Carey Bagdassarian who studied membrane defects, Rony Granek and Yardena Bohbot-Raviv who applied sophisticated statistical thermodynamic theory to analyze the behavior of liquid crystalline phases of self-assembled aggregates.
Back home, in the early 1980s, still in close collaboration with Bill Gelbart and in parallel to our work on the phase behavior of micelles and membranes, we begun an intensive research effort on the microscopic (intra-molecular) aspects of self-assembled amphiphilic aggregates. Quite a few students and postdocs have been involved in this research, beginning with Igal Szleifer who contributed to the application and later also the development of our theory of Amphiphile Chain Packing in micelles and membranes, continuing with Diego Kramer's work on phase transitons in monolayes, and then both Igal and Diego, with contributions from Didier Roux and Sam Safran we applied our chain packing theory to derive the Curvature Elasic Moduli of Lipid Membranes. With Debbie Hornreich-Fattal we studied the role of hydrophobic mismatch in lipid-protein interaction, and together with David Andelman the Vesicle-Micelle Transition. Daniel Harries provided new insights into the molecular aspects of chain packing in membranes, and and Sylvio May who first came to Jeruslaem as a graduate student Minerva fellow, and later on as a postdoc, has been very instrumental and creative in developing Compression-Type Models models of membrane elasticity and later their application to lipid-protein interactions and phase transitions. Many insights and ideas relevant to our work on membranes during these years were due to meetings and discussons with Erich Sackmann.
A different topic of my reasearch in the 1980s has been The Role of Adsorbate Lateral Interactions on the Kinetics and Thermodynamics of Catlytic Surface Reactions. Together with my friend and colleague Frank Rebentrost, and the graduate students Marvin Silverberg, and then Oren Becker, and then Yitzhak Farbman-Yogev, we analyzed the effects of Adsorbate Islanding revaling how they change the usual Power Laws prevailing in surface reaction kinetics.
In the late 1990s and early 2000s, together with Sylvio May and Daniel Harries, and largely inspired by the beautiful experiments of Safinya's group at UCSB, we have published a number of comprehensive articles explaining, predicting and analyzing (in very good agreement with experiment) the Structure and Phase Behavior of Lipoplexes, those Complexes of Cationic Llipid Membranes and DNA that were developed as vectors of DNA in gene delivery. To this end, an Extended Poisson-Boltzmann theory has been developed allowing to take into account, self-consistently, the effects of Lipid Lateral Mobility on the elctrostatic interactions between the DNA and the lipid membrane. An important qualitative conclusion was that the Entropic Gain upon Counterion Release is the major driving force of lipoplex formation. We also showed that counerion release combined "counter-lipid" release play major roles in various other Macroion (e.g., DNA or protein)-Membrane Interaction Phenomena. A few years later, with Assi Zemel and Sylvio May we studied the interaction of anti-microbial, amphipathic peptides with lipid membranes, revealing the conditions leading to pore formation.
The MARCKS protein plays a major role in numerous biological phenomena. It comprises a basic (effector) domain, flanked by two long intrinsically disordered amino-acid chains, one of which ends with a myristolytaed membrane anchor. As part of Shelly Tzlil's PhD work, around 2007 -- largely inspired by experiments and model studies of Stuart McLaughlin and coworkers -- we have theoretically analyzed the interaction of MARCKS with 2D-fluid membranes containing both monovalent (PS) and muli-valent (PIP2) acidic lipids, correctly predicting the structure and the subtle energetic comeponents of this interaction. An important theoretical-computational "by-product" of this study has been the development of an elaborate Monte-Carlo simulation algorithm, extending the Rosenbluth-method of polymer growth by taking into account, self-consistenly, the simulatenous motion and adjustment of the charged lipid distribution in the membrane. The same phenomenon has later been studied in collaboration with Vladimir Teif using the transfer matrix formalism.
Around the year 2000, encouraged by my highly enthusiatic friend Bill Gelbart, we became interested in Viruses, more precisely - in the Physics of Viruses. Our first goal in this field was to calculate the Forces and Pressures involved in the Pacakging and Release of DNA Into and Out of Bacterial Virus Capsids. Using a continuum theory developed with Shelly Tzlil and Brownian Dynamics simulations designed by James Kindt we determined the ("coil to spool") structure of the DNA in the capsid of the phage, and calculated the free energy of the the virus as a function the ejected genome length, finding very good agreement with the (roughly simultaneously published) single molecule measurements of Smith, Bustamante and their coworkers. We also predicted (as conjectured by Eric Raspaud) that increasing the osmotic pressure in solution can inhibit the ejection of the genome from the capsid. Soon afterwards this prediction has been amply and impressively corroborated experimetally by Alex Evilevitch, Bill Gelbart-and Chuck Knobler, following which my friend Bill turned into an entusiastic experimental physico-chemical-virolo-biologist.
Since around 2005 my theoretical virus-physics research, in close collaboration with the, by now mainly experimental, UCLA virus group, has mainly been concerned with RNA In and Out of Viral Capsids. All the work on this topic was done in close collaboration with UCLA students, most of whom spent long visits in Jerusalem. First, in his PhD work Aron Yoffe has shown that viral RNAs (packaged in icosahedral capsids) are Invariably More Compact than Non-Vral RNAs of the same nucleotide sequence length. We have also explained why The Ends of RNA are Always Close to Each Other. With Li Tai Fang we developed a Simple Model for RNA Folding that correctly predicts the average length of base-pair duplexes as well as the overall fraction of base pairing. Using Kramers formula for the radius of gyration of ideal branched polymers we also showed that Rg of Random-Sequence RNAs Scale as N(1/3) . Then, with Surendra Walter (aka David) Singaram we presented a theoretical explanation of the RNA Packaging Competition Experiments carried out at the UCLA lab. In addition, with Walter and Ajay Gopal we have used the Pruefer Shuffling Algorithm of Tree Graphs to show that While Branched Random Sequence RNA are Less Compact (Rg~N(1/3)) Than Ideal Randomly Branched Polymers ((Rg~N(1/4)) .
The PhD work of my last graduate student in Jerusalem, Yifat Brill-Karnielly, has dealt with the Mechanisms of Actin Polymerization and Branching. Collaborating with the Group of Ann Bernheim we propsed a theoretical model for the Role of Arp2/3 Branched Actin Network in Mediating the Formation of Flopodiya-Like Bundles. In yet another study Yifat showed how Actin Filaments Step-Wise Associate into Thicker Filopodia Bundles.
Finally I should mention the very fruitful collaboration with another friend of mine, Barry Honig, with whom, jointly with Larry Shapiro and members of their groups, but especially with Barry's postdoc at the time, Yinghao Wu, we studied various Statistical Thermodynamics Aspects of Cadherin Mediated Inter-Cell Adhesion. Two of the major topics studied were: First, the Essential Role of Cis Interaction between Trans-Bound Cadherin Dimers in Promoting Inter-Cell Junctions. The second topic has been concerned with extending Bell's theory of the Relationship between Receptor Binding in 2D vs. 3D, by taking into account the detailed structural characteristics of cadherin dimerization recently revealed in the Shapiro-Honig Lab.
Additional details of the research can of course be found in the attached publications. Furthermore, from the many power point (and older style) presentations given during my years of research I have assembled five collections of slides, covering - mostly graphically - some of the topics outlined above.